title: Granulocyte depletion attenuates sustained pulmonary hypertension and increased pulmonary vasoreactivity caused by continuous air embolization in sheep.
abstract: Chronic pulmonary hypertension can develop in diseases associated with acute or repeated inflammation in the lungs, e.g., adult respiratory distress syndrome, chronic bronchitis. Inflammation has also been associated with some animal models of chronic pulmonary hypertension. We have previously shown that 12 days of continuous air embolization into sheep results in the functional and structural changes of chronic pulmonary hypertension. To determine whether granulocytes contribute to these changes, five sheep were granulocyte-depleted with hydroxyurea immediately before and during air embolization (AIR-PMN) and were compared with sheep receiving air embolization (AIR only). Air embolization was discontinued briefly every 4 days for monitoring of pulmonary vascular pressures and assessment of pulmonary vasoreactivity to a bolus injection of PGH2-A. After 12 days of air embolization, the lungs were removed for structural studies. AIR-PMN sheep did not develop the sustained increase in pulmonary artery pressure seen in the AIR sheep (Day 12, AIR-PMN = 20 +/- 3 cm H2O; AIR = 29 +/- 2; mean +/- SE). Similarly, the increased pulmonary pressor response to PGH2-A seen in AIR sheep was not found in the AIR-PMN group. Structural studies of the barium-injected lungs of AIR-PMN sheep revealed a twofold increase in medial thickness of normally muscular arteries and a significant increase in the percent of muscular intraacinar arteries (similar to findings in lungs from AIR sheep). The number of barium-filled arteries was increased in AIR-PMN sheep when compared with that in AIR sheep, but the number was still less than in the control sheep. We conclude that granulocytes may contribute to the functional changes of chronic pulmonary hypertension after continuous air embolization in sheep, but they do not play a role in structural changes involving pulmonary arterial smooth muscle cells and their precursors. The present data also suggest that the reduction in peripheral arterial filling is the structural alteration that contributes most to the sustained rise in pulmonary artery pressure. The data further suggest that pulmonary hypertension after air embolization may have a vasoconstrictive component that is granulocyte-dependent.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.
authors.forename: E A
authors.initials: EA
authors.lastname: Perkett
authors.forename: K L
authors.initials: KL
authors.lastname: Brigham
authors.forename: B
authors.initials: B
authors.lastname: Meyrick
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004618:Embolism, Air / Q000097:blood / Q000150:complications* / Q000503:physiopathology / Q000662:veterinary; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology*; D006918:Hydroxyurea / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000097:blood / Q000209:etiology* / Q000503:physiopathology / Q000662:veterinary; D008168:Lung / Q000473:pathology; D008196:Lymph / Q000502:physiology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D012756:Sheep; D012757:Sheep Diseases / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; C062931:prostaglandin H2 9-cyclic ether; D044262:Prostaglandin H2; D006918:Hydroxyurea